ArticleMolecules (Basel, Switzerland)2022
AVA-NP-695 Selectively Inhibits ENPP1 to Activate STING Pathway and Abrogate Tumor Metastasis in 4T1 Breast Cancer Syngeneic Mouse Model.
Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Tanshinone IIA&Icaritin -MPs regulated vascular normalization and restored tumor-infiltrating T lymphocyte function to boost anti-PD-1 therapy in melanoma lung metastasis.Journal of nanobiotechnology · 2026Article
- The role of the intratumoral microbiota in breast cancer metastasis and immune regulation: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Unlocking the therapeutic potential of the STING signaling pathway in anti-tumor treatment.Clinical and experimental medicine · 2025Review
- Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors.Nature communications · 2025Article
- Enpp1 ameliorates MAFLD by regulating hepatocyte lipid metabolism through the AMPK/PPARα signaling pathway.Cell & bioscience · 2025Article
- Role of ENPP1 in cancer pathogenesis: Mechanisms and clinical implications (Review).Oncology letters · 2024Review
- Second messenger 2'3'-cyclic GMP-AMP (2'3'-cGAMP): the cell autonomous and non-autonomous roles in cancer progression.Acta pharmacologica Sinica · 2024Review
- Harnessing innate immune pathways for therapeutic advancement in cancer.Signal transduction and targeted therapy · 2024Review
- Small molecule innate immune modulators in cancer therapy.Frontiers in immunology · 2024Review
- Discovery of VH domains that allosterically inhibit ENPP1.Nature chemical biology · 2024Article
- DNA sensing in cancer: Pro-tumour and anti-tumour functions of cGAS-STING signalling.Essays in biochemistry · 2023Review
- Progress towards Adjuvant Development: Focus on Antiviral Therapy.International journal of molecular sciences · 2023Review
- Tailoring therapies to counter the divergent immune landscapes of breast cancer.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
11 authors.
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Abstract
Cyclic GMP-AMP synthase (cGAS) is an endogenous DNA sensor that synthesizes cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP) from ATP and GTP. 2'3'-cGAMP activates the stimulator of interferon genes (STING) pathway, resulting in the production of interferons and pro-inflammatory cytokines. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the phosphodiesterase that negatively regulates the STING pathway by hydrolyzing 2'3'-cGAMP. It has been established that the cGAS-STING pathway plays a major role in inhibiting tumor growth by upregulating T cell response. Herein, we demonstrate that AVA-NP-695, a selective and highly potent ENPP1 inhibitor, apart from the immunomodulatory effect also modulates cancer metastasis by negatively regulating epithelial-mesenchymal transition (EMT). We established that the combined addition of 2'3'-cGAMP and AVA-NP-695 significantly abrogated the transforming growth factor beta (TGF-ꞵ)-induced EMT in MDA-MB-231 cells. Finally, results from the in vivo study showed superior tumor growth inhibition and impact on tumor metastasis of AVA-NP-695 compared to Olaparib and PD-1 in a syngeneic 4T1 breast cancer mouse model. The translation of efficacy from in vitro to in vivo 4T1 tumor model provides a strong rationale for the therapeutic potential of AVA-NP-695 against triple-negative breast cancer (TNBC) as an immunomodulatory and anti-metastatic agent.
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